Potassium Carbonate → 3-(3-{3-[2-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-pyridin-4-ylmethyl]-5-isopropyl-2,6-dioxo-1,2,3,6-tetrahydro-pyrimidine-4-carbonyl}-5-methyl-phenyl)-acrylonitrile

HRID 426219Notes

Reaction equation

HRID 426219 reaction equation
[CH:1]([C:4]1[C:9](=[O:10])[NH:8][C:7](=[O:11])[NH:6][C:5]=1[C:12]([C:14]1[CH:15]=[C:16]([CH:21]=[CH:22][C:23]#[N:24])[CH:17]=[C:18]([CH3:20])[CH:19]=1)=[O:13])([CH3:3])[CH3:2].C(=O)([O-])[O-].[K+].[K+].[I-].[Li+].[C:33]1(=[O:51])[N:37]([C:38]2[CH:43]=[C:42]([CH2:44]Cl)[CH:41]=[CH:40][N:39]=2)[C:36](=[O:46])[C:35]2=[CH:47][CH:48]=[CH:49][CH:50]=[C:34]12>CN(C=O)C>[O:51]=[C:33]1[C:34]2[C:35](=[CH:47][CH:48]=[CH:49][CH:50]=2)[C:36](=[O:46])[N:37]1[C:38]1[CH:43]=[C:42]([CH2:44][N:6]2[C:5]([C:12]([C:14]3[CH:15]=[C:16]([CH:21]=[CH:22][C:23]#[N:24])[CH:17]=[C:18]([CH3:20])[CH:19]=3)=[O:13])=[C:4]([CH:1]([CH3:3])[CH3:2])[C:9](=[O:10])[NH:8][C:7]2=[O:11])[CH:41]=[CH:40][N:39]=1

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 66321Lithium iodideHCID 591846992-[4-(Chloromethyl)-2-pyridinyl]-1H-isoindole-1,3(2H)-dioneHCID 667053903-[3-(5-Isopropyl-2,6-dioxo-1,2,3,6-tetrahydro-pyrimidine-4-carbonyl)-5-methyl-phenyl]-acrylonitrile

Product 1

HCID 667055303-(3-{3-[2-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-pyridin-4-ylmethyl]-5-isopropyl-2,6-dioxo-1,2,3,6-tetrahydro-pyrimidine-4-carbonyl}-5-methyl-phenyl)-acrylonitrileYield 27%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of 3-[3-(5-isopropyl-2,6-dioxo-1,2,3,6-tetrahydro-pyrimidine-4-carbonyl)-5-methyl-phenyl]-acrylonitrile (323 mg, 1 mmol), anhydrous powdered potassium carbonate (138 mg, 1 mmol), lithium iodide (134 mg, 1 mmol), and 2-phthalimido-4-chloromethylpyridine, was added anhydrous DMF (5 ml) and the mixture was stirred for overnight at room temperature. The mixture was evaporated in vacuo and the residue was purified by silica gel column chromatography (eluent, EA:hexane (1:1)) to afford 152 mg (27%) of a white solid. 1H-NMR (200 MHz, DMSO-d6) δ 1.01 (3H, d, J=6.8 Hz), 1.10 (3H, d, J=6.8 Hz), 2.12 (1H, m), 2.33 (3H, s), 4.76 (2H, s), 6.57 (1H, d, J=16.6 Hz), 7.25 (1H, d, J=5.2 Hz), 7.31 (1H, s), 7.61 (1H, d, J=16.6 Hz), 7.80 (1H, s), 7.88-8.02 (6H, m), 8.41 (1H, d, J=5.2 Hz), 11.72 (1H, s).

Workup

  1. customThe mixture was evaporated in vacuo
  2. customthe residue was purified by silica gel column chromatography (eluent, EA:hexane (1:1))

Sources & evidence

ORD record
ord-a1e0c20d22b54cae8e5ccae424321998
Source dataset
uspto-grants-2012_01
Patent number
US08106064B2

Reaction notes

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